Lethal giant larvae‐1 deficiency enhances the CD8+ effector T‐cell response to antigen challenge in vivo

Lethal giant larvae‐1 (Lgl‐1) is an evolutionary conserved protein that regulates cell polarity in diverse lineages; however, the role of Lgl‐1 in the polarity and function of immune cells remains to be elucidated. To assess the role of Lgl‐1 in T cells, we generated chimeric mice with a hematopoietic system deficient for Lgl‐1. Lgl‐1 deficiency did not impair the activation or function of peripheral CD8+ T cells in response to antigen presentation in vitro, but did skew effector and memory T‐cell differentiation. When challenged with antigen‐expressing virus or tumor, Lgl‐1‐deficient mice displayed altered T‐cell responses. This manifested in a stronger antiviral and antitumor effector CD8+ T‐cell response, the latter resulting in enhanced control of MC38‐OVA tumors. These results reveal a novel role for Lgl‐1 in the regulation of virus‐specific T‐cell responses and antitumor immunity.